Ovarian cancer is the fifth leading cause of death from cancer in US women. In most instances, a diagnosis is not made until the cancer is in an advanced state, at a time when the five year survival rate of patients is only about 28% (Ries, et al., SEERC Cancer Stat. Rev. 1973-1995 (1998)). In contrast, the five year survival rate for women diagnosed with localized disease is about 95%. These statistics provide an incentive to search for new diagnostic tests for this disease, especially those that can be used in screening patients and which may detect cancer at an early stage.
Over the last several years, efforts at the discovery of biomarkers for ovarian cancer have focused primarily on serum and plasma. Relatively little attention has been paid to urinary biomarkers despite advantages that urine-based tests have in terms of non-invasiveness, convenience and cost. Although urine assays have been traditionally used for urinary tract diseases, more recent studies have indicated that these assays are also valuable in the detection of other diseases as well (Pisitkun, et al., Mol. Cell. Proteomics 5:1760-1771 (2006)) including lung cancer (Tantipaiboonwong, et al., Proteomics 5:1140-1149 (2005) and breast cancer (Roy, et al., J. Biol. Chem. 279:51323-51330 (2004)). Assays of glycosylated forms of eosinophil-derived neurotoxin and COOH-terminal peptides of osteopontin in urine have been found to be associated with ovarian cancer malignancy (Ye, et al., Clin. Cancer Res. 12:432-441 (2006); Chambers, et al., Clin. Cancer Res. 12:323-327 (2006); U.S. Pat. No. 7,288,383; US 2005009120).
The most commonly used plasma assay for detecting ovarian cancer is for the CA125 biomarker. However this test is of limited sensitivity and is poor at detecting ovarian cancer in its early stages, when the disease is most treatable. These limitations may be, at least in part, due to the complicated structure of the CA125 protein and interference from high levels of other plasma proteins. An assay of urine for peptides generated during the breakdown of CA125 may avoid these problems and would be well suited to the widespread screening of patients.